Studies on obstruction-induced hypertrophy of the urinary bladder smooth muscle, produced by partial ligation of the urethra in rabbits, show increased SM1 myosin heavy chain isoform, gamma-actin, and 1- caldesmon (non-muscle specific). Changes in the composition of these proteins, that are involved in muscle contraction and in cytoplasmic motile activities, are associated with decreased ability of the obstructed bladder to empty. The proposed study is focused to understand the biochemical, cellular, and molecular mechanisms that regulate the urinary bladder function and dysfunction, associated with bladder diseases. Experiments are designed to determine how the motile and contractile activities of the smooth muscle cells in the detrusor muscle are regulated in normal urinary bladder muscle, and how they are altered.in response to increased functional demand impinged upon the bladder muscle due to the pathophysiological processes. The data from the experiments proposed in this renewal application will enable us to test the following hypotheses: 1. hypertrophy is associated with a difference in the regulation of actin-myosin interaction and actomyosin ATPase, 2. obstruction-induced hypertrophy of the bladder mass is associated with an alteration in the regulation of monomeric myosin I, which is involved in intracellular functions that require motility, and 3. the increase in functional demand for bladder muscle contraction associated with outlet obstruction up regulates the expression of myosin heavy chain isoform SM1 and other smooth muscle specific proteins, such as gamma-actin and caldesmon, in bladder muscle. These data will also help to determine if the alteration in caldesmon, observed in hypertrophied urinary bladder, is associated with an alteration in the regulation of monomeric myosin I, which is involved in intracellular functions that require motility. Experiments on cultured bladder smooth muscle cells will provide the basic data that is necessary to study the transcriptional regulation of contractile proteins which are altered in response to obstruction-induced bladder hypertrophy.